Since the dawn of civilization, elemental gold and gold compounds have been revered and utilized by Shamen and medical practitioners alike for many varied pathological problems. In the 20(th) century following the observations of Jacques Forestier, injectable gold compounds were successfully used for the treatment of rheumatoid arthritis. Of the many compounds developed, gold sodium thiomalate has been the most extensively studied by basic scientists and by clinicians. In the1980s, the oral gold compound auranofin showed promise as a therapeutic contender to injectable gold, but the clinical side effect profile and fear of long term effects of immune suppression by auranofin, resulted in gold sodium thiomalate continuing as the preferred gold compound for rheumatoid treatment. However, the increased use and demonstration of effectiveness of low dose Methotrexate (MTX) in rheumatoid treatment over the last 20 years has resulted in a significant decline in the use of injectable gold sodium thiomalate, this despite the claims and evidence that it remains a useful agent in the management of rheumatoid arthritis. Several authors still contend that the injectable gold compounds can still play a valuable role, and indeed may be the correct first choice in the management of rheumatoid arthritis.

Clinical pharmacology of gold.

Using a novel high performance liquid chromatography (HPLC) determination of ascorbic acid and dehydroascorbic acid, we have measured the relative amounts of ascorbate and dehydroascorbate in 20 normal controls and in paired sera and synovial fluid from 13 patients with rheumatoid arthritis (RA). In complete contrast to previous published findings we were able to detect dehydroascorbate in normal human sera (12.0 +/- 3.7 mumol/l), while the mean and range of ascorbate measured in normals was 69.6 +/- 20.6 mumol/l. These findings were completely reversed in rheumatoid sera (21.8 +/- 8.6 mumol/l and 5.1 +/- 5.0 mumol/l for dehydroascorbate and ascorbic acid respectively). In several rheumatoid sera no ascorbate could be detected. In paired synovial fluid and serum samples, there was always more dehydroascorbate detected in synovial fluids than in the corresponding sera (p less than 0.01). The data suggests that the reduced level of ascorbate and increased level of dehydroascorbate may be a reflection of the increased antioxidant and free-radical scavenging activity of the vitamin in RA, especially within the inflamed joint.

The Determination of Dehydroascorbic Acid and Ascorbic acid in the Serum and Synovial Fluid of Patients with Rheumatoid Arthritis (RA)

Effect of deoxycortone and ascorbic acid on formaldehyde-induced arthritis in normal and adrenalectomised rats

The literature on experimental scurvy capillary fragility blood ascorbic acid levels urinary excretion studies and other attempts to measure the need for Vitamin-C in human beings is surveyed. Some animal studies are also included. Factors that may affect Vitamin-C requirements are environmental temperature and pressure (requirements are higher in cold climates) physical exertion tobacco smoking wound healing infection allergenic reactions and hormonal function. The literature on endocrine function and Vitamin-C interaction is conflicting. Some studies have found decreased blood ascorbic acid levels during the menstrual cycle some increases midway through the cycle and some no change. 1 study reported distinct decreases at time of ovulation. 4 experimental subjects taking oral contraceptives showed low plasma ascorbic acid levels during ovulation and high during the men ses while controls showed just the reverse pattern. Since the drugs are not administered during the menses it was suggested oral contraceptives depress plasma ascorbic acid concentration. Some studies suggest Vitamin-C supplements for women taking oral contraceptives while others show that the Vitamin-C level remains low in spite of the supplements. Possible changes in intestinal absorption in metabolism and utilization or in excretion under the influence of sex hormones is suggested. Observations of Addisons disease suggests a relationship between Vitamin-C deficiency and adrenal function. A study showed that under stress or when adrenocorticotrophic hormone (ACTH) was administere d the adrenal was promptly depleted of ascorbic acid. Administration of 500 mg/day Vitamin-C is accompanied by a significant increase in level of 17-hydroxycorticosteroids in the blood and 17-ketosteroids in the urine. Various suggestions have been made to explain this relationship. There is also a relationship between Vitamin-C and mental health. Requirements of specific population groups are given including: premature and full-term infants preschool and school age children adolescents pregnant and lactating women and the elderly.

A conspectus of research on vitamin C requirements of man.

Bonta, Sorenson and others have shown that Cu(II) derivatives are effective anti-inflammatory agents. Some chemical and pharmacological properties of Cu(I) and metallic Cu are discussed. Thio complexes of Cu(I) were prepared and shown to be useful anti-inflammatory agents in rats. Hypotheses are stated concerning the possible therapeutic value of copper in its various oxidation states.

Copper and inflammation

SummaryThe blood plasma ascorbic acid (reduced form) in active cases of rheumatoid arthritis is regularly low if the individuals have not been maintained on a high vitamin C supplement. Unadvised cases were found to show uniformly lowered levels. The reduction is striking. Such levels rise in response to extra supplements of vitamin C. In many this rise is refractory. Our studies indicate that in some cases the intake required to maintain adequate vitamin C levels in the plasma are much above the average requirement for normal individuals. The mechanism involved is unexplained.

Reduced Ascorbic Acid Content of Blood Plasma in Rheumatoid Arthritis.

Controlled evaluation of gold therapy in rheumatoid arthritis.

Physical therapy is an important therapeutic agent for patients with rheumatoid arthritis. Well directed exercise balanced with rest is fundamental. Careful muscular reeducation is as important in the treatment of patients with arthritis as it is in caring for a patient with paralysis. Pain with slight malalignment and limitation in the joint will cause muscles to lose their sequence of action and so upset the rhythm of motion.

Active exercise with a balanced use of assistance and resistance to movement, combined, as indicated, with traction upon the joint or stretching of constricted tissues may result in (1) stabilization of the joint, (2) increase in range of movement, (3) relaxation of antagonists, and (4) reduction of atrophy. The objectives of muscular exercise then are (1) reduction of pain, spasm and deformity, (2) development of muscular power, and (3) restoration of the normal rhythm of movement.

Rheumatoid arthritis. Present-day physical therapy.

On the basis of the occurrence of gross and microscopic changes in the articular tissues of guinea pigs subjected to subacute or chronic scurvy, either alone or in combination with infection, we made the suggestion that vitamin C deficiency may be a significant contributory mechanism in the etiology of some cases of rheumatoid or atrophic arthritis. 1 Brief but suggestive clinical evidence was presented at that time. Subsequently we have endeavored to investigate the problem thoroughly in the clinic. Detailed dietary histories were taken in as many cases as possible. What we consider to be a deficient intake of vitamin C has been a common though not universal finding. A detailed analysis of these records will be made and published later. The belief that nutritional factors may be important in this disease is not new. Many writers have stressed the importance of nutrition. Hall 2 said: "We are constantly seeing

Metabolism of vitamin c in rheumatoid arthritis

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Reduced Ascorbic Acid Content of Blood Plasma in Rheumatoid Arthritis.

Controlled evaluation of gold therapy in rheumatoid arthritis.

Rheumatoid arthritis. Present-day physical therapy.

Metabolism of vitamin c in rheumatoid arthritis